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Tang PM, Bui-Xuan NH, Wong CK, et al. Pheophorbide a-Mediated Photodynamic Therapy Triggers HLA Class I-Restricted Antigen Presentation in Human Hepatocellular Carcinoma. Transl Oncol. 2010;3(2):114-22doi: 10.1593/tlo.09262.
Tang, P. M., Bui-Xuan, N. H., Wong, C. K., Fong, W. P., & Fung, K. P. (2010). Pheophorbide a-Mediated Photodynamic Therapy Triggers HLA Class I-Restricted Antigen Presentation in Human Hepatocellular Carcinoma. Translational oncology, 3(2), 114-22. https://doi.org/10.1593/tlo.09262
Tang, Patrick Ming-Kuen, et al. "Pheophorbide a-Mediated Photodynamic Therapy Triggers HLA Class I-Restricted Antigen Presentation in Human Hepatocellular Carcinoma." Translational oncology vol. 3,2 (2010): 114-22. doi: https://doi.org/10.1593/tlo.09262
Tang PM, Bui-Xuan NH, Wong CK, Fong WP, Fung KP. Pheophorbide a-Mediated Photodynamic Therapy Triggers HLA Class I-Restricted Antigen Presentation in Human Hepatocellular Carcinoma. Transl Oncol. 2010 Apr;3(2):114-22. doi: 10.1593/tlo.09262. PMID: 20360936; PMCID: PMC2847319.
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Transl Oncol. 2010 Apr;3(2):114-22. doi: 10.1593/tlo.09262.

Pheophorbide a-Mediated Photodynamic Therapy Triggers HLA Class I-Restricted Antigen Presentation in Human Hepatocellular Carcinoma.

Translational oncology

Patrick Ming-Kuen Tang, Ngoc-Ha Bui-Xuan, Chun-Kwok Wong, Wing-Ping Fong, Kwok-Pui Fung

Affiliations

  1. School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.

PMID: 20360936 PMCID: PMC2847319 DOI: 10.1593/tlo.09262

Abstract

The immunomodulatory effects of photodynamic therapy (PDT) have been reported in several photosensitizers. Pheophorbide a (Pa), a chlorophyll derivative, shows antitumor effects on a number of human cancers in a PDT approach (Pa-PDT); however, the potential effect of Pa-PDT on the anticancer immunity has never been studied. In the present work, the underlying action mechanism of Pa-PDT was systemically investigated with a human hepatoma cell line HepG2. We found that Pa-PDT significantly inhibited the growth of HepG2 cells with a half maximal inhibitory concentration/endoplasmic reticulum of 0.35 microM at 24 hours by the induction of apoptosis, as shown by externalization of phosphatidylserine, release of mitochondrial cytochrome c, and activation of the caspases cascade in the treated cells. Interestingly, using two-dimensional polyacrylamide gel electrophoresis analysis, a 57-kDa disulfide-isomerase-like ER resident protein (ERp57) that belongs to the HLA class I-restricted antigen-processing machinery was found to be mediated during the Pa-PDT treatment. This activation of antigen presentation was confirmed by Western blot analysis and immunostaining. Furthermore, a cross-presentation of antigen with HLA class I proteins and 70-kDa heat shock protein was found in Pa-PDT-treated cells, as shown by the confocal microscopic observation and immunoprecipitation assay. Nevertheless, the immunogenicity of HepG2 cells was increased by Pa-PDT treatment that triggered phagocytic capture by human macrophages. Our findings provide the first evidence that Pa-PDT can trigger both apoptosis and cancer immunity in the tumor host.

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